A theoretical model of the ionosphere dynamics with interhemispheric coupling

Dynamic model for ionospheric plasma with interhemispheric couplin

A general enantioselective route to the chamigrene natural product family

Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented

Modelling ultrasound-induced mild hyperthermia of hyperplasia in vascular grafts

<p>Abstract</p> <p>Background</p> <p>Expanded polytetrafluoroethylene (ePTFE) vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. We modelled the selective absorption of ultrasound by ePTFE, and explored the feasibility of preventing hyperplasia in ePTFE grafts by ultrasound heating. Specifically, we simulated the temperature profiles of implanted grafts and nearby soft tissues and blood under ultrasound exposure. The goal was to determine whether ultrasound exposure of an ePTFE graft can generate temperatures sufficient to prevent cell growth on the graft without damaging nearby soft tissues and blood.</p> <p>Methods</p> <p>Ultrasound beams from two transducers (1.5 and 3.2 MHz) were simulated in two graft/tissue models, with and without an intra-graft cellular layer mimicking hyperplasia, using the finite-difference time-domain (FDTD) method. The resulting power deposition patterns were used as a heat source for the Pennes bioheat equation in a COMSOL^®Multiphysics heat transfer model. 50°C is known to cause cell death and therefore the transducer powers were adjusted to produce a 13°C temperature rise from 37°C in the ePTFE.</p> <p>Results</p> <p>Simulations showed that both the frequency of the transducers and the presence of hyperplasia significantly affect the power deposition patterns and subsequent temperature profiles on the grafts and nearby tissues. While neither transducer significantly raised the temperature of the blood, the 1.5-MHz transducer was less focused and heated larger volumes of the graft and nearby soft tissues than the 3.2-MHz transducer. The presence of hyperplasia had little effect on the blood's temperature, but further increased the temperature of the graft and nearby soft tissues in response to either transducer. Skin cooling and blood flow play a significant role in preventing overheating of the native tissues.</p> <p>Conclusions</p> <p>Modelling shows that ultrasound can selectively heat ePTFE grafts and produce temperatures that cause cell death on the graft. The temperature increase in blood is negligible and that in the adjacent soft tissues may be minimized by skin cooling and using appropriate transducers. Therefore, ultrasound heating may have the potential to reduce neointimal hyperplasia and failure of ePTFE vascular grafts.</p

Families' social backgrounds matter : socio-economic factors, home learning and young children's language, literacy and social outcomes

Parental support with children's learning is considered to be one pathway through which socio-economic factors influence child competencies. Utilising a national longitudinal sample from the Millennium Cohort Study, this study examined the relationship between home learning and parents' socio-economic status and their impact on young children's language/literacy and socio-emotional competence. The findings consistently showed that, irrespective of socio-economic status, parents engaged with various learning activities (except reading) roughly equally. The socio-economic factors examined in this study, i.e., family income and maternal educational qualifications, were found to have a stronger effect on children's language/literacy than on social-emotional competence. Socio-economic disadvantage, lack of maternal educational qualifications in particular, remained powerful in influencing competencies in children aged three and at the start of primary school. For children in the first decade of this century in England, these findings have equity implications, especially as the socio-economic gap in our society widens

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival

Risk Factors for Triple-Negative Breast Cancer in Women Under Age 45

Little is known about the etiologic profile of triple-negative breast cancer (negative for estrogen receptor/progesterone receptor/human epidermal growth factor), a breast cancer subtype associated with high mortality and inadequate therapeutic options. We undertook this study to assess the risk for triple-negative breast cancer among women 45 years of age and younger in relation to demographic/lifestyle factors, reproductive history, and oral contraceptive use. Study participants were ascertained in two previous population-based, case-control studies. Eligible cases included all primary invasive breast cancers among women ages 20 to 45 years in the Seattle-Puget Sound area, diagnosed between January 1983 and December 1992, for whom complete data was obtained for estrogen receptor, progesterone receptor, and human epidermal growth factor status (n = 897; including n = 187 triple-negative breast cancer cases). Controls were age matched and ascertained via random digit dialing. Oral contraceptive use >/=1 year was associated with a 2.5-fold increased risk for triple-negative breast cancer (95% confidence interval, 1.4-4.3) and no significantly increased risk for non-triple-negative breast cancer (Pheterogeneity = 0.008). Furthermore, the risk among oral contraceptive users conferred by longer oral contraceptive duration and by more recent use was significantly greater for triple-negative breast cancer than non-triple-negative breast cancer (Pheterogeneity = 0.02 and 0.01, respectively). Among women /=1 year was 4.2 (95% confidence interval, 1.9-9.3), whereas there was no significantly increased risk with oral contraceptive use for non-triple-negative breast cancer among women </=40 years, nor for triple-negative breast cancer or non-triple-negative breast cancer among women 41 to 45 years of age. In conclusion, significant heterogeneity exists for the association of oral contraceptive use and breast cancer risk between triple-negative breast cancer and non-triple-negative breast cancer among young women, lending support to a distinct etiology

Amino Acid Stability in the Early Oceans

It is likely that a variety of amino acids existed in the early oceans of the Earth at the time of the origin and early evolution of life. "Primordial soup", hydrothermal vent, and meteorite based processes could have contributed to such an inventory. Several "protein" amino acids were likely present, however, based on prebiotic synthesis experiments and carbonaceous meteorite studies, non-protein amino acids, which are rare on Earth today, were likely the most abundant. An important uncertainty is the length of time these amino acids could have persisted before their destruction by abiotic and biotic processes. Prior to life, amino acid concentrations in the oceans were likely regulated by circulation through hydro-thermal vents. Today, the entire ocean circulates through vent systems every 10(exp 7) years. On the early Earth, this value was likely smaller due to higher heat flow and thus marine amino acid life-time would have been shorter. After life, amino acids in the oceans could have been assimilated by primitive organisms

Do breast implants after a mastectomy affect subsequent prognosis and survival?

In a large study, published in this issue of Breast Cancer Research, Le and colleagues report that women receiving implants after mastectomies for early-stage breast cancer experience lower breast cancer mortality than women not receiving implants. Assessment of survival patterns among women receiving reconstructive implants is complex given unique patient characteristics, disease attributes, and treatment patterns. The interpretation of reduced mortality from breast cancer must be assessed in light of significantly reduced risks of death from most other causes. In contrast, patients receiving post-mastectomy implants had elevated rates of suicide, consistent with findings among women with cosmetic implants. Additional well-designed investigations are needed to clarify survival patterns among women receiving reconstructive implants